Oncology Central

Tumor location in metastatic colorectal cancer: predictive or prognostic?

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Dr Hafez Halawani talks to Oncology Central regarding  the predictive and prognostic potential of tumor location in metastatic colorectal cancer  – a debate that was perpetuated with the presentation of the Venook et al study at the 2016 ASCO meeting. Read on to discover more about previously established predictive markers in metastatic colorectal cancer, the evidence linking tumor location and survival, and Halawani’s opinion on whether this evidence will ever influence clinical practice.

Could you please introduce yourself and tell us a little about your career to date?

My name is Hafez Halawani; I am a medical oncologist/hematologist by training and I graduated from Tufts University Western campus in 2002. I worked in Alexandria, LA, USA, then moved to King Fahad Specialist Hospital in Dammam, Saudi Arabia, where I was the Chairman of Medical Oncology. I was then appointed as the Acting Director of the Cancer Center. Currently, I am the head of the colorectal oncology group at King Fahad Specialist Hospital – Dammam.

What are the current treatment options & the associated challenges in overall management of metastatic colorectal cancer?

In metastatic colorectal cancer (mCRC), combination chemotherapy with or without biologics – anti-EGFR and anti-VEGF agents – has become the standard practice for patients with good performance status.

At the time of diagnosis, tumors have to be tested for RAS (KRAS and NRAS) mutations to determine whether they would be candidates for anti-EGFR therapy. Patients with RAS wild-type in all loci seem to benefit the most when treated with combination chemotherapy and anti-EGFR agents.

BRAF testing is not yet standard practice where BRAF-mutant tumor patients may benefit from more intensive chemotherapy. Microsatellite instability (MSI) is also not current standard practice, although tumors with high levels of MSI may benefit from immunotherapy with anti-PD-1/PD-L1 agents.

What methods are currently utilized to predict survival in mCRC? Are there any current predictive markers that influence treatment decisions?

One of the most challenging decisions is what therapy to choose for your patient. There are conflicting data in patients with RAS wild-type; while the FIRE-3 and PEAK trials favored chemotherapy and anti-EGFR over chemotherapy and anti-VEGF, a larger trial CALGB-80405 showed no difference.

A more intensive therapy with oxaliplatin, irinotecan, 5-fluorouracil and leucovorin, in addition to anti-VEGF, was shown to be superior to FOLFIRI plus anti-VEGF in an Italian study, so where would that fit in our armamentarium?.

The only prognostic factor in mCRC that is agreed upon is BRAF status, where tumors with mutated BRAF have a worse prognosis regardless of the treatment they get. RAS on the other hand, is known to be predictive, where patients with RAS wild-type receiving chemotherapy with anti-EGFR have a better prognosis than those who receive chemotherapy alone.

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